Trial of Tadalafil, Tamsulosin and Combination for Access Sheath Deployment

• Status: Enrolling by invitation
• Trial end date: 2022-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Extensive literature exists on the use of alpha-blocker medications for the removal of kidney stones. Alpha blockers relax certain muscles and help small blood vessels remain open. They work by keeping the hormone norepinephrine (noradrenaline) from tightening the muscles in the walls of smaller arteries and veins, which causes the vessels to remain open and relaxed. This improves blood flow and lowers blood pressure. There are studies that demonstrate alpha-blockers decrease ureteral pressure and help the ureter "relax."

Recent studies have shown that phosphodiesterase inhibitors may also help with ureteral stone passing. A phosphodiesterase inhibitor is a drug that blocks an enzyme that inhibits relaxation of smooth muscle. This means that it can help smooth muscle, such as the muscle that lines the ureter, to relax. While ureteral relaxation is helpful in the passage of ureteral stones, our study seeks to use this finding by pretreating participants with an older generation alpha blocker or a phosphodiesterase inhibitor prior to passage of a ureteral access sheath in cases in which ureteroscopy is being used to approach a ureteral or renal stone.

By relaxing the ureter, it is possible that a larger access sheath can be safely placed. This may allow for facilitating passage of the ureteroscope and extraction of stone fragments while precluding the development of potentially damaging intrarenal pressure from the flow of irrigant. The ureteral access sheath also protects the ureter from damage during the procedure. Placement of the largest access sheath possible is helpful in that larger stone fragments can be retrieved, the flow of irrigant is improved, and the surgical field is kept clear of blood or debris. To date, nobody has studied whether use of an uro-selective alpha blocker, alone, or in combination with a 5 phosphodiesterase inhibitor will result in passage of larger access sheaths.

In this study participants will be randomized into 1 of 4 categories: Flomax (alpha-blocker), Cialis (5-phosphodiesterase inhibitor), a combination of the 2, or a placebo arm. In this study the placebo, or no active drug, is the current standard of care and will serve as a control from the other 3 groups.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Irvine
• Treatments: Adrenergic alpha-Antagonists; Phosphodiesterase 5 Inhibitors; Tadalafil; Tamsulosin

Criteria

Inclusion Criteria:

• Patients undergoing percutaneous nephrolithotomy (PCNL) or ureteroscopy (URS) for renal or proximal ureteral urolithiasis

• A documented sterile urine culture within 1-2 weeks of the procedure

• ≥ 18 years old

• Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

• Patients < 18-years-old

• Presence of ureteral stent or nephrostomy tube prior to scheduled procedure

• Patients requiring open, endoscopic, or laparoscopic procedure in the same setting as the intended URS or PCNL

• Planned concurrent bilateral endoscopic ureteral procedures

• Patients currently taking alpha-blockers within 14 days of surgery

• Patients taking PDE-5 inhibitors within 14 days of surgery

• Pregnant women

• Active urinary tract infection (UTI) or uncontrolled HIV

• Uncorrected coagulopathy

• Patients who cannot stop their blood thinners, and/or non-steroidal anti-inflammatory medications 5-7 days prior to the procedure

• Patients allergic to tamsulosin or tadalafil

• Patients with upcoming cataract surgery due to risk of floppy iris syndrome

• Patients with history of priapism

• Patients with hereditary retinitis pigmentosa

• Patients concurrently using nitrates for myocardial infarction (MI) or angina

• Patients with high risk cardiovascular disease: left ventricular outflow obstruction, MI in last 90 days, unstable angina, stroke in last 6 months, uncontrolled arrhythmias

• Patients with renal impairment (CrCl < 30 mL/min) or severe hepatic impairment (Child-Pugh score ≥ 10)

• Patients using CYP3A4 inhibitors such as clarithromycin, ritonavir, ketoconazole, or Iitraconazole